A magnetic beads-based ligand fishing method for rapid discovery of monoterpene indoles as monoamine oxidase A inhibitors from Hunteria zeylanica.

In this study, a novel magnetic bead-based ligand fishing method was developed for rapid discovery of monoterpene indoles as monoamine oxidase A inhibitors from natural products. In order to improve the screening efficiency, two different magnetic beads, i.e. amine and carboxyl terminated magnetic beads, were comprehensively compared in terms of their ability to immobilize monoamine oxidase A (MAOA), biocatalytic activity and specific adsorption rates for affinity ligands. Carboxyl terminated magnetic beads performed better for MAOA immobilization and demonstrated superior performance in ligand fishing. The MAOA immobilized magnetic beads were applied to screen novel monoamine oxidase inhibitors in an alkaloid-rich plant, Hunteria zeylanica. Twelve MAOA affinity ligands were screened out, and ten of them were identified as monoterpene indole alkaloids by HPLC-Obitrap-MS/MS. Among them, six ligands, namely geissoschizol, vobasinol, yohimbol, dihydrocorynanthenol, eburnamine and (+)-isoeburnamine which exhibited inhibitory activity against MAOA with low IC50 values. To further explore their inhibitory mechanism, enzyme kinetic analysis and molecular docking studies were conducted.

Detecting mental and physical disorders using multi-task learning equipped with knowledge graph attention network.

Mental and physical disorders (MPD) are inextricably linked in many medical cases; psychosomatic diseases can be induced by mental concerns and psychological discomfort can ensue from physiological diseases. However, existing medical informatics studies focus on identifying mental or physical disorders from a unilateral perspective. Consequently, no existing domain knowledge base, corpus, or detection modeling approach considers mental as well as physical aspects concurrently. This paper proposes a joint modeling approach to detect MPD. First, we crawl through online medical consultation records of patients from websites and build an MPD knowledge ontology by extracting the core conceptual features of the text. Based on the ontology, an MPD knowledge graph containing 12,673 nodes and 82,195 relations is obtained using term matching with a domain thesaurus of each concept. Subsequently, an MPD corpus with fine-grained severities (None, Mild, Moderate, Severe, Dangerous) and 8909 records is constructed by formulating MPD classification criteria and a data annotation process under the guidance of domain experts. Taking the knowledge graph and corpus as the dataset, we design a multi-task learning model to detect the MPD severity, in which a knowledge graph attention network (KGAT) is embedded to better extract knowledge features. Experiments are performed to demonstrate the effectiveness of our model. Furthermore, we employ ontology-based and centrality-based methods to discover additional potential inferred knowledge, which can be captured by KGAT so as to improve the prediction performance and interpretability of our model. Our dataset has been made publicly available, so it can be further used as a medical informatics reference in the fields of psychosomatic medicine, psychiatrics, physical co-morbidity, and so on.

Health risk assessment for human mercury exposure from Cinnabaris-containing Baizi Yangxin Pills in healthy volunteers Po administration.

BACKGROUND: Cinnabaris (α-HgS), a mineral traditional Chinese material medica, has been used in combination with other herbs manifesting some definite therapeutic effects for thousands of years. But the currently reported mercury poisoning incidents raised the doubts about the safety of Cinnabaris-containing traditional Chinese medicines (TCMs). Baizi Yangxin Pills (BZYXP) is a Cinnabaris-containing TCM widely used in clinical practice. This study evaluated the health risk of mercury exposure from BZYXP in healthy volunteers based on the total mercury and mercury species analysis of blood and urine after single and multiple doses of BZYXP. METHODS: Blood pharmacokinetics and urinary excretion studies of mercury were compared between single (9 g, once daily) and multiple doses (9 g, twice daily, continued for 7 days) of BZYXP. The whole blood and urine samples were collected at the specific points or periods after the administration of BZYXP. The total mercury and mercury species in blood and urine samples were determined by cold vapor-atomic fluorescence spectrometry (CV-AFS) and HPLC-CV-AFS, respectively. RESULTS: The mercury was excreted slowly and accumulated obviously after continuous exposure of BZYXP. Moreover, the well-known neurotoxin methylmercury (MeHg) was detected in blood samples after 7 days' administration of BZYXP. In the urine samples, only Hg(II) was detected. Therefore, long-term use of BZYXP will cause mercury poisoning due to mercury's high accumulative properties and MeHg formation. CONCLUSION: Cinnabaris-containing TCMs such as BZYXP should be restricted to cases in which alternatives are available, and the blood mercury species profile should be monitored during the long-term clinical medication.

Valproate use associated with frontal and cerebellar gray matter volume reductions: A voxel-based morphometry study.

Recent morphometric magnetic resonance imaging (MRI) studies suggested the possibility that valproate (VPA) use is associated with parieto-occipital cortical thinning in patients with heterogeneous epilepsy syndromes. In this study, we examined the effect of VPA on the brain volume using a large number of homogenous patients with idiopathic generalized epilepsy. Voxel-based morphometry was used to compare regional gray matter (GM) volume between 112 patients currently taking VPA (VPA+ group), 81 patients not currently taking VPA (VPA- group), and 120 healthy subjects (control group). The VPA+ group showed a significant GM volume reduction in the bilateral cerebellum, hippocampus, insula, caudate nucleus, medial frontal cortex/anterior cingulate cortex, primary motor/premotor cortex, medial occipital cortex, and anteromedial thalamus, as compared to the control group. The VPA- group showed a significant GM volume reduction in the anteromedial thalamus and right hippocampus/temporal cortex, as compared to the control group. Compared to the VPA- group, the VPA+ group had a significant GM volume reduction in the bilateral cerebellum, primary motor/premotor cortex, and medial frontal cortex/anterior cingulate cortex. We have provided evidence that VPA use could result in GM volume reductions in the frontal cortex and cerebellum. Our findings should be acknowledged as a potential confounding factor in morphometric MRI studies that include subjects taking VPA.

Evaluation of pharmacological and pharmacokinetic herb-drug interaction between irinotecan hydrochloride injection and Kangai injection in colorectal tumor-bearing mice and healthy rats.

Introduction: Kangai (KA) injection, a Chinese herbal injection, is often used in combination with irinotecan (CPT-11) to enhance the effectiveness of anti-colorectal cancer treatment and alleviate side effects. However, the combined administration of this herb-drug pair remains controversial due to limited pre-clinical evidence and safety concerns. This study aimed to determine the pre-clinical herb-drug interactions between CPT-11 and KA injection to provide a reference for their clinical co-administration. Methods: In the pharmacological study, BALB/c mice with CT26 colorectal tumors were divided into four groups and treated with vehicle alone (0.9% saline), CPT-11 injection (100 mg/kg), KA injection (10 mL/kg), or a combination of CPT-11 and KA injection, respectively. The tumor volume of mice was monitored daily to evaluate the therapeutic effect. Daily body weight, survival rate, hematopoietic toxicity, immune organ indices, and gut toxicity were analyzed to study the adverse effects. Healthy Sprague-Dawley rats in the pharmacokinetic study were administered KA injection only (4 mL/kg), or a combination of CPT-11 injection (20 mg/kg) and KA injection, respectively. Six key components of KA injection (oxymatrine, matrine, ginsenoside Rb1, Rg1, Re, and astragaloside IV) in rat plasma samples collected within 24 h after administration were determined by LC-MS/MS. Results: The pharmacological study indicated that KA injection has the potential to enhance the anti-colorectal cancer efficacy of CPT-11 injection and alleviate the severe weight loss induced by CPT-11 injection in tumor-bearing mice. The pharmacokinetic study revealed that co-administration resulted in inhibition of oxymatrine metabolism in rats, evidenced by the significantly reduced Cmax and AUC0-t of its metabolite, matrine (p < 0.05), from 2.23 ± 0.24 to 1.38 ± 0.12 µg/mL and 8.29 ± 1.34 to 5.30 ± 0.79 µg h/mL, respectively. However, due to the similar efficacy of oxymatrine and matrine, this may not compromise the anti-cancer effect of this herb-drug pair. Discussion: This study clarified the pre-clinical pharmacology and pharmacokinetic benefits and risks of the CPT-11-KA combination and provided a reference for their clinical co-administration.

Animal efficacy study of a plant extract complex (BEN815) as a potential treatment for COVID-19.

In a short time, several types of injectable and oral therapeutics have been developed and used to effectively manage patients with coronavirus disease 2019 (COVID-19). BEN815 is an improved mixture of three extracts (Psidium guajava, Camellia sinensis, and Rosa hybrida) recognized by the Ministry of Food and Drug Safety of Korea as a health food ingredient that alleviates allergic rhinitis. The current animal efficacy study was performed to assess its probability of improving COVID-19 symptoms. BEN815 treatment significantly increased the survival of K18-hACE2 transgenic mice and reduced viral titers in the lungs at 5 days post infection (DPI). Furthermore, the lungs of the treated mice showed mild tissue damage at 5 DPI and nearly complete recovery from COVID-19 at 14 DPI. BEN815 appears to be an effective and minimally toxic anti-SARS-CoV-2 agent in mice and has potential for clinical applications.

Gemcitabine enhances pharmacokinetic exposure of the major components of Danggui Buxue Decoction in rat via the promotion of intestinal permeability and down-regulation of CYP3A for combination treatment of non-small cell lung cancer.

CONTEXT: Danggui Buxue Decoction (DBD), a traditional Chinese medicine formula, has the potential to enhance the antitumor effect of gemcitabine in non-small cell lung cancer (NSCLC) treatment by increasing gemcitabine's active metabolites. However, whether gemcitabine affects the pharmacokinetics of DBD's major components remains unclear. OBJECTIVE: This study evaluates the herb-drug interaction between DBD's major components and gemcitabine and validates the underlying pharmacokinetic mechanism. MATERIALS AND METHODS: The pharmacokinetics of 3.6 g/kg DBD with and without a single-dose administration of 50 mg/kg gemcitabine was investigated in Sprague-Dawley rats. The effects of gemcitabine on intestinal permeability, hepatic microsomal enzymes in rat tissues, and CYP3A overexpressing HepG2 cells were determined using western blot analysis. RESULTS: The combination of gemcitabine significantly altered the pharmacokinetic profiles of DBD's major components in rats. The Cmax and AUC of calycosin-7-O-ß-d-glucoside notably increased through sodium-glucose transporter 1 (SGLT-1) expression promotion. The AUC of ligustilide and ferulic acid was also significantly elevated with the elimination half-life (t1/2) prolonged by 2.4-fold and 7.8-fold, respectively, by down-regulating hepatic CYP3A, tight junction proteins zonula occludens-1 (ZO-1) and occludin expression. DISCUSSION AND CONCLUSIONS: Gemcitabine could modulate the pharmacokinetics of DBD's major components by increasing intestinal permeability, enhancing transporter expression, and down-regulating CYP3A. These findings provide critical information for clinical research on DBD as an adjuvant for NSCLC with gemcitabine and help make potential dosage adjustments more scientifically and rationally.

Epidemiology of mumps, mumps complications, and mumps orchitis in Korea using the National Health Insurance Service database.

PURPOSE: To analyze the presentation of mumps and mumps orchitis using the National Health Insurance Service Database (NHISD). MATERIALS AND METHODS: Using information from the NHISD representing all cases of mumps in Korea, data regarding mumps orchitis were analyzed. The International Classification of Diseases, Tenth Revision, and Clinical Modification codes were used for diagnosis. The incidence estimates of the number of mumps cases were analyzed using the Statistical Analysis System (SAS) software. RESULTS: Based on the NHISD, 199,186 people were diagnosed with mumps, and males accounted for 62.3% cases. Teen males accounted for 69,870 cases, the largest number of patients diagnosed with mumps. The annual incidence of mumps increased every year (poisson regression, hazard ratio [HR] 1.026, 95% confidence interval [CI] 1.024-1.027; p<0.025). The risk of mumps was lower in females than that in males (poisson regression, HR 0.594, 95% CI 0.589-0.599; p<0.001). Of the 199,186 patients diagnosed with mumps, 3,872 patients (1.9%) had related complications. Among the mumps complications, the most diagnosed complication was mumps orchitis, which was seen in 41.8% of the males. Mumps orchitis cases accounted for less than 1.5% of the patients with mumps in minors under the age of 20 years and was somewhat higher in 2009 and 2013-2015. CONCLUSIONS: Among the complications related to mumps, meningitis was most common in females, while orchitis was dominant in males. Mumps orchitis also shows periodic outbreaks but is particularly prevalent in adults, which suggests the potential need for additional vaccination against mumps.

Chaihu-Longgu-Muli decoction improves sleep disorders by restoring orexin-A function in CKD mice.

Introduction: Chaihu-Longgu-Muli decoction (CLMD) is a well-used ancient formula originally recorded in the "Treatise on Febrile Diseases" written by the founding theorist of Traditional Chinese Medicine, Doctor Zhang Zhongjing. While it has been used extensively as a therapeutic treatment for neuropsychiatric disorders, such as insomnia, anxiety and dementia, its mechanisms remain unclear. Methods: In order to analyze the therapeutic mechanism of CLMD in chronic renal failure and insomnia, An adenine diet-induced chronic kidney disease (CKD) model was established in mice, Furthermore, we analyzed the impact of CLMD on sleep behavior and cognitive function in CKD mice, as well as the production of insomnia related regulatory proteins and inflammatory factors. Results: CLMD significantly improved circadian rhythm and sleep disturbance in CKD mice. The insomnia related regulatory proteins, Orexin, Orexin R1, and Orexin R2 in the hypothalamus of CKD mice decreased significantly, while Orexin and its receptors increased remarkably after CLMD intervention. Following administration of CLMD, reduced neuron loss and improved learning as well as memory ability were observed in CKD mice. And CLMD intervention effectively improved the chronic inflflammatory state of CKD mice. Discussion: Our results showed that CLMD could improve sleep and cognitive levels in CKD mice. The mechanism may be related to the up-regulation of Orexin-A and increased phosphorylation level of CaMKK2/AMPK, which further inhibits NF-κB downstream signaling pathways, thereby improving the disordered inflammatory state in the central and peripheral system. However, More research is required to confirm the clinical significance of the study.

Systematic evaluation of combined herbal adjuvant therapy for proliferative diabetic retinopathy.

Objective: To evaluate the efficacy and safety of combined traditional Chinese medicine in the adjuvant treatment of proliferative diabetic retinopathy (PDR) by Meta-analysis. Methods: PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang databases were searched by computer. Random controlled clinical trials (RCTS) using traditional Chinese medicine as adjuvant therapy for proliferative diabetic retinopathy were screened, and Stata16.0 software was used to perform meta-analysis on the final included literatures. Results: A total of 18 studies involving 1392 patients were included. Meta-analysis showed that the clinical effective rate OR=2.99 (CI: 2.18-4.10, I2 = 42.7%, P<0.05); Visual acuity MD=0.10(CI: 0.06-0.13, I2 = 0%, P<0.05); Fundus efficacy OR=5.47 (CI: 1.33-22.51, I2 = 71.4%, P<0.05); Neovascularisation regression rate OR=8 (CI: 3.83-16.71, I2 = 30.1%, P<0.05); Macular foveal thickness MD=-44.24 (CI: -84.55-3.93, I2 = 95.6%, P<0.05); Absorption of vitreous hemorrhage OR=4.7 (CI: 2.26-9.77, I2 = 0%, P<0.05); Fasting blood glucose MD=-0.23, (CI: -0.38-0.07, I2 = 0%, P<0.05); 2h postprandial blood glucose MD=-0.19 (CI: -0.52-0.14, I2 = 0%, P=0.25). From the results, the combined Chinese medicine adjuvant therapy showed better efficacy than the control group. A total of 69 kinds of traditional Chinese medicine were involved in 18 studies, among which the top four applied frequencies were Panax notoginseng, Rehmannia rehmannii, Astragalus membranaceus and Poria cocos. Most of the medicines were sweet and bitter in taste, the qi tended to be slight cold and cold, and the meridian tropism belongs to the liver meridian. Conclusion: The combination of traditional Chinese medicine adjuvant therapy has a good curative effect on PDR patients. However, the relevant clinical trials are few and more high-quality clinical trials are still needed, what's more the attention should be paid to the exploration of its safety.

[Identification and expression of uridine diphosphate glycosyltransferase(UGT) gene family from Dendrobium officinale].

Uridine diphosphate glycosyltransferase(UGT) is a highly conserved protein in plants, which usually functions in secondary metabolic pathways. This study used the Hidden Markov Model(HMM) to screen out members of UGT gene family in the whole genome of Dendrobium officinale, and 44 UGT genes were identified. Bioinformatics was used to analyze the structure, phylogeny, and promoter region components of D. officinale genes. The results showed that UGT gene family could be divided into four subfamilies, and UGT gene structure was relatively conserved in each subfamily, with nine conserved domains. The upstream promoter region of UGT gene contained a variety of cis-acting elements related to plant hormones and environmental factors, indicating that UGT gene expression may be induced by plant hormones and external environmental factors. UGT gene expression in different tissues of D. officinale was compared, and UGT gene expression was found in all parts of D. officinale. It was speculated that UGT gene played an important role in many tissues of D. officinale. Through transcriptome analysis of D. officinale mycorrhizal symbiosis environment, low temperature stress, and phosphorus deficiency stress, this study found that only one gene was up-regulated in all three conditions. The results of this study can help understand the functions of UGT gene family in Orchidaceae plants and provide a basis for further study on the molecular regulation mechanism of polysaccharide metabolism pathway in D. officinale.

[A new dihydrochalcone from Humulus scandens].

To study the chemical constituents from the stems and leaves of Humulus scandens, this study isolated thirteen compounds by different chromatographic methods including silica gel column, ODS, Sephadex LH-20 and preparative HPLC. Based on comprehensive analysis, the chemical structures were elucidated and identified as citrunohin A(1), chrysosplenetin(2), casticin(3), neoechinulin A(4), ethyl 1H-indole-3-carboxylate(5), 3-hydroxyacetyl-indole(6),(1H-indol-3-yl) oxoacetamide(7), inonotusic acid(8), arteannuin B(9), xanthotoxol(10), α-tocopherol quinone(11), eicosanyl-trans-p-coumarate(12), and 9-oxo-(10E,12E)-octadecadienoic acid(13). Among them, compound 1 was a new dihydrochalcone, and the other compounds were obtained from H. scandens for the first time.

Evaluation of the Antiviral Efficacy of Subcutaneous Nafamostat Formulated with Glycyrrhizic Acid against SARS-CoV-2 in a Murine Model.

The ongoing COVID-19 pandemic highlights the urgent need for effective antiviral agents and vaccines. Drug repositioning, which involves modifying existing drugs, offers a promising approach for expediting the development of novel therapeutics. In this study, we developed a new drug, MDB-MDB-601a-NM, by modifying the existing drug nafamostat (NM) with the incorporation of glycyrrhizic acid (GA). We assessed the pharmacokinetic profiles of MDB-601a-NM and nafamostat in Sprague-Dawley rats, revealing rapid clearance of nafamostat and sustained drug concentration of MDB-601a-NM after subcutaneous administration. Single-dose toxicity studies showed potential toxicity and persistent swelling at the injection site with high-dose administration of MDB-601a-NM. Furthermore, we evaluated the efficacy of MDB-601a-NM in protecting against SARS-CoV-2 infection using the K18 hACE-2 transgenic mouse model. Mice treated with 60 mg/kg and 100 mg/kg of MDB-601a-NM exhibited improved protectivity in terms of weight loss and survival rates compared to the nafamostat-treated group. Histopathological analysis revealed dose-dependent improvements in histopathological changes and enhanced inhibitory efficacy in MDB-601a-NM-treated groups. Notably, no viral replication was detected in the brain tissue when mice were treated with 60 mg/kg and 100 mg/kg of MDB-601a-NM. Our developed MDB-601a-NM, a modified Nafamostat with glycyrrhizic acid, shows improved protectivity against SARS-CoV-2 infection. Its sustained drug concentration after subcutaneous administration and dose-dependent improvements makes it a promising therapeutic option.

Crude polysaccharide from Danggui Buxue decoction enhanced the anti-tumor effect of gemcitabine by remodeling tumor-associated macrophages.

Tumor-associated macrophages (TAMs) with an M2-phenotype mediate gemcitabine resistance to cancer by influencing the metabolic enzymes of gemcitabine and releasing competitive deoxycytidine (dC). Our previous studies showed that Danggui Buxue Decoction (DBD), a traditional Chinese medicinal recipe, enhances the anti-tumor activity of gemcitabine in vivo and alleviates gemcitabine-induced myelosuppression. However, the material basis and exact mechanism underlying its enhanced effects remain unclear. In this study, a bioactive polysaccharide consisting of arabinose, mannose, ribose, and glucose was isolated from DBD. In vivo results demonstrated that DBD crude polysaccharide (DBDP) ameliorated gemcitabine-induced immune system disorders. Moreover, DBDP improved the sensitivity of Lewis lung carcinoma-bearing mice to gemcitabine by reshaping the tumor-promoting M2-like macrophages into tumor-inhibiting M1-phenotypes. Furthermore, in vitro results further revealed that DBDP blocked the protective effects of TAMs and M2-macrophages against gemcitabine by inhibiting the excessive secretion of dC and decreasing the high expression of cytidine deaminase. In conclusion, our results demonstrated that DBDP, as the pharmacodynamic material basis of DBD, enhanced the anti-tumor activity of gemcitabine against lung cancer in vitro and in vivo, which was associated with remodeling of the M2-phenotype.

Effect of Multimodal Exercise on Cancer-Related Fatigue in Patients Undergoing Simultaneous Radiotherapy and Chemotherapy: A Randomized Trial in Patients with Breast Cancer.

Background and Objective: Breast cancer as well as the main treatments for breast cancer, including radiotherapy and chemotherapy, cause cancer-related fatigue in up to 90% of patients, seriously reducing the quality of life of patients. So, the study aimed to explore the intervention effect of multimodal exercise on cancer-related fatigue in patients with breast cancer. Methods: One hundred and eighty-four breast cancer patients who were receiving simultaneous radiotherapy and chemotherapy in a grade 3A specialist hospital in Shandong Province were randomly divided into an experimental group (n = 92) and a control group (n = 92). The experimental group received routine radiotherapy and chemotherapy nursing and additional multimodal exercise training, whereas the control group received only routine radiotherapy and chemotherapy nursing. The evaluation tools used were the general information questionnaire, cancer-related fatigue scale, hospital anxiety and depression scale, and quality of life scale for cancer patients. The scores for cancer-related fatigue, anxiety, depression, and quality of life were measured before and 1, 3, and 5 weeks after intervention. Results: The total score for cancer-related fatigue was significantly lower in the experimental group than in the control group (P < .05). Conclusion: Multimodal exercise can effectively relieve the fatigue symptoms of patients with breast cancer during radiotherapy and chemotherapy, reduce depression, and improve the quality of life.

Metabolomic Responses of Lettuce (Lactuca sativa) to Allelopathic Benzoquinones from Iris sanguinea Seeds.

Weed management is important in modern crop protection. Chemical weed control using synthetic herbicides, however, suffers from resistance and ecotoxicity. Metabolomic investigation of allelopathy (or allelochemicals) may provide novel alternatives to synthetic herbicides. This study aimed to investigate the detailed metabolomic responses of plants to allelochemicals in Iris seed extracts. The seed extracts of Iris sanguinea showed the strongest growth inhibitory activity against alfalfa, barnyard grass, lettuce, and mustard. 3-Hydroxyirisquinone (3-[10(Z)-heptadecenyl]-2-hydroxy-5-methoxy-1,4-benzoquinone) was isolated as a major allelochemical from I. sanguinea seeds through bioassay-guided fractionation. The compound inhibited the growth of shoots and roots by browning root tips. Discriminant analysis identified 33 differentially regulated lettuce metabolites after treatment with 3-hydroxyirisquinone (3HIQ). Metabolic pathway analysis revealed that several metabolic pathways, including aromatic amino acid biosynthesis and respiratory pathways, were affected by the compounds. Differential responses of membrane lipids (accumulation of unsaturated fatty acids) and extensive formation of reactive oxygen species were observed in root tissues following treatment with 3HIQ. Overall, alkylbenzoquinone from I. sanguinea induced extensive metabolic modulation, oxidative stress, and growth inhibition. The metabolomic responses to allelochemicals may provide fundamental information for the development of allelochemical-based herbicides.

The efficacy and safety of Chinese herbal medicine in the treatment of painful diabetic neuropathy: A systematic review and meta-analysis.

Objective: The objective of this systematic review and meta-analysis is to assess the effectiveness and security of Chinese herbal medicine (CHM) in the therapy of painful diabetic neuropathy (PDN). Methods: We searched databases for randomized controlled trials (RCTs) of CHM in the treatment of PDN. Outcome indicators included nerve conduction velocity, clinical efficiency, pain score, TCM syndrome score, and adverse events. Stata 16.0 was used to carry out the Meta-analysis. Results: A total of 21 RCTs with 1,737 participants were included. This meta-analysis found that using CHM as adjuvant treatment or as monotherapy for PDN can improve SCV of median nerve [mean difference (MD) = 3.56, 95% Confidence interval (CI) (2.19, 4.92) ], MCV of median nerve [ MD = 3.82, 95% CI (2.51, 5.12) ], SCV of common peroneal nerve [ MD = 4.16, 95% CI (1.62, 6.70) ], MCV of common peroneal nerve [ MD = 4.37, 95% CI (1.82, 6.93) ], SCV of gastrocnemius nerve [ MD = 4.95, 95% CI (3.52, 6.37) ], SCV of tibial nerve [ MD = 3.17, 95% CI (-2.64, 8.99) ], MCV of tibial nerve [MD = 6.30, 95%CI (5.00, 7.60)] and clinical effective rate [ odds ratio (OR) = 4.00, 95% CI (2.89, 5.52) ] and reduce pain score [standardized mean difference (SMD) = -2.23, 95% CI (-3.04, -1.41) ], TCM syndrome score [ MD = -4.70, 95% CI (-6.61, -2.80) ]. In addition, compared to the control group, adverse events of Chinese medicine intervention occurred less. Conclusion: CHM as adjuvant therapy or single treatment has a good curative effect and is safe for patients with PDN, which is worthy of clinical promotion and use, however; higher quality clinical studies are still needed to prove. Systematic Review Registration: https://www.crd.york.ac.uk/, identifier CRD42022327967.

Network Pharmacological Analysis and Animal Experimental Study on Osteoporosis Treatment with GuBen-ZengGu Granules.

Aim: We explored the molecular pathway and material basis of GuBen-ZengGu granules (GBZGG) in treating osteoporosis using network pharmacology and animal experiments. Methods: The effective active components and potential targets of GBZGG were obtained from the TCMSP database and BATMAN-TCM database. Disease-related genes were obtained from GeneCard, NCBI, and DisGeNET. Next, a protein interaction network was established using the STRING database, and core genes were screened using the MCODE module. Cytoscape 3.8.0 was used to construct the network of component-disease-pathway-target, and KEGG pathway enrichment analyses were performed using the clusterProfiler R package to predict the mechanism of GBZGG in treating osteoporosis. An osteoporosis rat model was established by ovarian excision (OVX), and the partial results of network pharmacology were experimentally verified. Results: Pharmacodynamic results showed that GBZGG increased bone mineral density (BMD) and significantly improved the indexes of femur microstructure in model rats. The network pharmacology results showed that quercetin, luteolin, stigmasterol, angelicin, kaempferol, bakuchiol, bakuchiol, 7-O-methylisomucronulatum, isorhamnetin, formononetin, and beta-sitosterol are the major components of GBZGG, with MAPK1, AKT1, JUN, HSP90AA1, RELA, MAPK14, ESR1, RXRA, FOS, MAPK8, NCOA1, MYC, and IL-6 as its core targets for treating osteoporosis. Biological effects could be exerted by regulating the signaling pathways of fluid shear stress and the signaling pathways of atherosclerosis, advanced glycation end products (AGE-RAGE) of diabetic complications, prostate cancer, interleukin (IL-17), tumor necrosis factor (TNF), hepatitis B, mitogen-activated protein kinase (MAPK), etc. The results of animal experiments showed that GBZGG could reduce the serum levels of IL-6 and TNF-α, increase the expression of bone morphogenetic protein-2 (BMP-2) and runt-related transcription factor 2 (RUNX2) protein, and inhibit the activity of extracellular-regulated protein kinases (ERK1/2) and phosphorylation ERK1/2 (p-ERK1/2) protein. Conclusion: GBZGG reduces the expression of ERK1/2 and p-ERK1/2 proteins and mRNAs through the inhibitory effects on IL-6 and TNF-α and negatively regulates the MAPK/ERK signaling pathway. The osteoporosis model showed that it effectively improved the loss of bone mass and destruction of bone microstructure in rats and maintained a positive balance for bone metabolism.

Mulberry leaf extract improves intestinal barrier function and displays beneficial effects on colonic microbiota and microbial metabolism in weaned piglets.

BACKGROUND: Mulberry leaf extract (MLE) extracted from mulberry leaves is rich in a variety of bioactive ingredients and can be used as feed additives of weaned piglets. The present study was conducted to evaluate the effects of dietary MLE supplementation on intestinal barrier function, colon microbial numbers and microbial metabolites of weaned piglets. RESULTS: MLE supplementation increased the villus height and the villus height/crypt depth ratio in jejunum and ileum (P < 0.05), increased the mRNA expression of ZO-1, Claudin-1 and MUC-2 in the ileal mucosa (P < 0.05), and decreased the serum level of lipopolysaccharide (P < 0.01). Meanwhile, MLE reduced the mRNA expression of tumor necrosis factor-α and interleukin-1ß (P < 0.05) and increased secretory immunoglobulin A level in the ileal mucosa (P < 0.05). In addition, MLE increased the numbers of beneficial bacteria Bifidobacterium and Lactobacillus (P < 0.05) and decreased the number of potential pathogenic bacteria Escherichia coli (P < 0.05) in the colon. Correspondingly, MLE supplementation reduced the pH value of colonic digesta (P < 0.05) and altered the microbial fermentation pattern of the colon by increasing the concentrations of microbial metabolites derived from carbohydrates fermentation such as lactate, acetate, butyrate and total short-chain fatty acids (P < 0.05), and decreasing the concentrations of microbial metabolites derived from amino acid fermentation such as p-cresol, skatole, spermine, histamine and tryptamine (P < 0.05). CONCLUSION: MLE supplementation improved intestinal barrier function and displayed beneficial effects on colon microbes and microbial metabolism in weaned piglets. © 2022 Society of Chemical Industry.

Co-treatment with Origanum Oil and Thyme Oil Vapours Synergistically Limits the Growth of Soil-borne Pathogens Causing Strawberry Diseases.

Vapours from origanum oil (O) and thyme oil (T) were applied to the four soil-borne strawberry pathogens Fusarium oxysporum f. sp. fragariae, Colletotrichum fructicola, Lasiodiplodia theobromae, and Phytophthora cactorum, causing Fusarium wilt, anthracnose, dieback, and Phytophthora rot, respectively. Increasing T vapour doses in the presence of O vapour strongly inhibited mycelial growths of the four pathogens and vice versa. When mycelia of F. oxysporum f. sp. fragariae and P. cactorum exposed to the combined O + T vapours were transferred to the fresh media, mycelial growth was restored, indicating fungistasis by vapours. However, the mycelial growth of C. fructicola and L. theobromae exposed to the combined O + T vapours have been slightly retarded in the fresh media. Prolonged exposure of strawberry pathogens to O + T vapours in soil environments may be suggested as an alternative method for eco-friendly disease management.